• Acute respiratory failure (ARF)
• biomarkers
• high-flow nasal oxygen (HFNO)
• non-invasive ventilation (NIV)
• pneumonia
• preventive strategies
• risk stratification
• vaccination

• Diagnosis
• Gastroesophageal reflux disease
• Management
• Pathophysiological mechanisms
• Risk factors

• Humans
• Gastroesophageal Reflux/diagnosis
• Gastroesophageal Reflux/therapy
• Gastroesophageal Reflux/epidemiology
• Gastroesophageal Reflux/physiopathology
• Global Health/statistics & numerical data
• Prevalence
• Risk Factors
• Treatment Failure

• CABG
• GDMT
• Guidelines
• TAVI
• antibiotics
• antiplatelet
• antithrombotic
• atrial fibrillation
• beta-blockers
• cardiac surgery
• coronary artery bypass grafting
• evidence based practice
• glucose management
• guideline directed medical therapy
• pain
• perioperative medication
• risk reduction
• secondary prevention
• statins
• steroids
• transcatheter aortic valve implantation
• valve replacement

• COVID-19
• infections
• prognosis
• proton pump inhibitors
• sepsis

• Proton Pumps/adverse effects
• Proton Pumps/therapeutic use
• Humans
• Male
• Female
• Adult
• Aged
• Aged, 80 and over
• Bacterial Infections/drug therapy
• Bacterial Infections/epidemiology
• Sepsis/drug therapy
• Sepsis/epidemiology
• COVID-19/complications
• COVID-19/epidemiology
• Hospital Mortality
• Intensive Care Units
• Prognosis
• Hospitalization

• critical care
• histamine H2-receptor antagonist
• patient discharge
• pediatric
• proton pump inhibitor
• stress ulcer prophylaxis

• Humans
• Proton Pump Inhibitors/therapeutic use
• Proton Pump Inhibitors/economics
• Cost-Benefit Analysis
• Aged
• Deprescriptions
• Quality-Adjusted Life Years
• Hong Kong
• Male
• Female
• Aged, 80 and over
• Cost-Effectiveness Analysis

• Antacids
• GERD
• H2-receptor antagonists
• P-CABs
• PPI

• geriatric medicine
• health services for the aged
• public health
• quality in health care

• Humans
• Republic of Korea/epidemiology
• Male
• Female
• Aged
• COVID-19/mortality
• COVID-19/epidemiology
• Retrospective Studies
• Prognosis
• Middle Aged
• Potentially Inappropriate Medication List/statistics & numerical data
• SARS-CoV-2
• Aged, 80 and over
• Critical Care/statistics & numerical data
• Inappropriate Prescribing/statistics & numerical data
• Registries

• National Research Foundation of Korea

• Humans
• Male
• Pulmonary Disease, Chronic Obstructive/therapy
• Pulmonary Disease, Chronic Obstructive/economics
• Pulmonary Disease, Chronic Obstructive/epidemiology
• Female
• Aged
• Retrospective Studies
• Hospitalization/economics
• Middle Aged
• Jordan/epidemiology
• Disease Progression
• Aged, 80 and over

• Deanship of Scientific Research, University of Jordan

• Bayes factors
• Bayesian
• Frequentist
• Meta-analysis
• Posterior probability

• Bayes Theorem
• Humans
• Randomized Controlled Trials as Topic/methods
• Randomized Controlled Trials as Topic/statistics & numerical data
• Meta-Analysis as Topic
• Non-Randomized Controlled Trials as Topic/methods
• Bias
• Models, Statistical

• cost-effectiveness
• fundoplication
• gastroesophageal reflux
• proton pump inhibitors

• Humans
• Gastroesophageal Reflux/surgery
• Fundoplication
• Treatment Outcome
• Time
• Laparoscopy

• HC17C0050 the Ministry of Health & Welfare

• acute kidney injury
• immune checkpoint inhibitors
• immune-related adverse events
• interstitial nephritis
• proton pump inhibitors

• K08 DK118120 NIDDK NIH HHS
• UL1 TR002377 NCATS NIH HHS
• Korea National Institute of Health
• NIDDK
• CCaTS

• Acinetobacter baumanii
• Klebsiella pneumoniae
• Pseudomonas aeruginosa
• carbapenem resistance
• coinfection
• multidrug resistance

• Adult
• Humans
• Klebsiella pneumoniae
• Pseudomonas aeruginosa
• Coinfection/drug therapy
• Coinfection/epidemiology
• Carbapenems/pharmacology
• Carbapenems/therapeutic use
• Carbapenem-Resistant Enterobacteriaceae
• Risk Factors
• Pneumonia/drug therapy
• Acinetobacter
• Klebsiella Infections/complications
• Klebsiella Infections/drug therapy
• Klebsiella Infections/epidemiology
• Anti-Bacterial Agents/pharmacology
• Anti-Bacterial Agents/therapeutic use

• adherence
• deprescription
• geriatric
• indication
• polypharmacy
• proton pump inhibitors
• rebound symptomatology
• therapeutic reconciliation

• drug dosage
• h2 receptor antagonist
• peptic ulcer disease
• proton pump inhibitors
• safety and efficacy

• COVID‐19
• acute kidney injury
• artificial respiration
• famotidine
• gastrointestinal hemorrhage
• mortality
• pantoprazole

• Humans
• Proton Pump Inhibitors/adverse effects
• Pancreaticoduodenectomy/adverse effects
• Gastroparesis/etiology
• Gastroparesis/prevention & control
• Retrospective Studies
• Peptic Ulcer/chemically induced
• Postoperative Complications/etiology
• Gastric Emptying

• P-CAB
• PPI
• dexlansoprazole
• esomeprazole
• lansoprazole
• omeprazole
• pantoprazole
• rabeprazole

• adverse outcomes
• histamine H2 receptor antagonists
• safety
• umbrella review

• Humans
• Infant, Newborn
• Histamine H2 Antagonists/adverse effects
• Pneumonia
• Enterocolitis, Necrotizing
• Proton Pump Inhibitors/adverse effects

• age
• intracerebral hemorrhage
• mortality
• sex

• electroacupuncture
• gastric mucosal injury
• repair factors
• severe neurological disease
• stress ulcer

• National Natural Science Foundation of China

• liver steatosis
• microbiota
• proton pump inhibitors

• K23 AR071473 NIAMS NIH HHS

• Dysphagia
• Esophageal motility
• Fundoplication
• Manometry
• Multiple rapid swallows

• Humans
• Deglutition Disorders/diagnosis
• Deglutition Disorders/etiology
• Fundoplication
• Retrospective Studies
• Manometry

• BMI, body mass index
• CI, confidence interval
• CT, computed tomography
• GERD
• GERD, gastroesophageal reflux disease
• OR, odds ratio
• RBC, red blood cell
• atrial arrhythmia
• hiatal hernia
• lobectomy
• lung cancer
• postoperative complications

• T32 CA233414 NCI NIH HHS
• T35 DK104689 NIDDK NIH HHS
• UL1 TR001863 NCATS NIH HHS

• Proton pump inhibitor (PPI)
• drug adverse effect
• glucocorticoid
• hospital-acquired pneumonia (HAP)
• retrospective cohort study

• Healthcare-associated infections
• Hospital-acquired pneumonia
• Infection prevention
• Pneumonia
• Risk factors

• COVID-19
• aerodigestive
• motility
• proton-pump inhibitor
• steroids

• COVID-19/epidemiology
• COVID-19 Testing
• Child
• Communicable Disease Control
• Humans
• Prospective Studies
• SARS-CoV-2

• R01 DK097112 NIDDK NIH HHS

• inhaled antibiotics
• respiratory tract infections
• tracheal aspirate

The development of drugs for the therapy of COVID-19 is one of the main problems of modern physiology, biochemistry and pharmacology. Taking into account the available information on the participation of mast cells and the role of histamine in the pathogenesis of COVID-19, as well as information on the positive role of famotidine in the prevention and treatment of coronavirus infection, an experiment was carried out using famotidine in a mouse model. We used a type A/PR/8/34 (H1N1) virus adapted to mice. The antiviral drug oseltamivir (Tamiflu), which belongs to the group of neuraminidase inhibitors, was used as a reference drug. The use of famotidine in combination with oseltamivir can increase survival, improve the dynamics of animal weight, reduce the level of NKT cells and increase the level of naive T-helpers. Further studies of famotidine in vivo should be aimed at optimizing the regimen of drug use at a higher viral load, as well as with a longer use of famotidine.

This study aimed to evaluate incidence risk and adverse clinical outcomes in COVID-19 disease among short-term users of acid-suppressants in South Korea.

This retrospective cohort study, conducted using a nationwide claims database for South Korea, used data from patients with COVID-19 tested between January 1 and May 15, 2020. Patients aged over 18 years and prescribed proton pump inhibitors (PPI) or histamine-2 receptor antagonist (H₂RA) for more than 7 days were identified. Primary outcome was COVID-19 while secondary outcomes were all-cause mortality, hospitalization with respiratory disease, or intensive respiratory intervention. Large-scale propensity scores were used to match patients, while the Cox proportional hazard model was utilized to evaluate any association between exposure and outcome(s). The risk estimates were calibrated by using 123 negative control outcomes.

We identified 26,166 PPI users and 62,117 H₂RA users. After propensity score matching, compared to H₂RA use, PPI use was not significantly associated with lower risk of COVID-19 (calibrated hazard ratio [HR], 0.81 [95% confidence interval (CI), 0.30–2.19]); moreover, PPI use was not associated with adverse clinical outcomes in COVID-19, namely, hospitalization with respiratory disease (calibrated HR, 0.88 [95% CI, 0.72–1.08]), intensive respiratory interventions (calibrated HR, 0.92 [95% CI, 0.46–1.82]), except for all-cause mortality (calibrated HR, 0.54 [95% CI, 0.31–0.95]).

In this study, we found that the PPI user was not associated with risk of COVID-19 compared to H₂RA users. There was no significant relationship between severe clinical outcomes of COVID-19 and exposure to PPI compared with H₂RA, except for all-cause mortality.

The online version contains supplementary material available at 10.1186/s40360-022-00549-7.

• Acid suppressants
• Epidemiology
• Pharmacovigilance
• Retrospective studies

• enteral nutrition
• histamine 2 receptor antagonists
• nutrition
• proton pump inhibitor
• stress ulcer
• stress ulcer prophylaxis

Long-term use of gastric-acid-suppressive drugs is known to be associated with several adverse effects. However, the association between enteric infection and acid suppression therapy is still uncertain. This study aimed to evaluate the association between gastric acid suppression and the risk of enteric infection. Materials and Methods: We conducted a population-based case-control study using the data from Chang Gung Research Database (CGRD) in Taiwan. Between January 2008 and December 2017, a total of 154,590 adult inpatients (age > 18) were identified. A pool of potential eligible controls according to four propensity scores matching by sex, age, and index year were extracted (n = 89,925). Subjects with missing data or who received less than 7 days of proton pump inhibitors (PPIs) and/or H2-receptor antagonists (H2RAs) were excluded. Finally, 17,186 cases and 69,708 corresponding controls were selected for analysis. The use of PPIs and H2RAs, the result of microbiological samples, and co-morbidity conditions have been analyzed. Confounders were controlled by conditional logistic regression. Results: 32.84% of patients in the case group used PPIs, compared with 7.48% in the control group. Of patients in the case group, 9.9% used H2RAs, compared with 6.9% in the control group. Of patients in the case group, 8.3% used a combination of PPIs and H2RAs, compared with 2.7% in the control group. The most common etiological pathogens were Enterococcus (44.8%), Clostridioides difficile (34.5%), and Salmonella spp. (10.2%). The adjusted odds ratio (OR) for PPI use with enteric infection was 5.526 (95% confidence interval [CI], 5.274–5.791). For H2RAs, the adjusted odds ratio was 1.339 (95% confidence interval [CI], 1.261–1.424). Compared to the control group, persons with enteric infection had more frequent acid-suppressive agent usage. Conclusions: This study demonstrates that gastric-acid-suppressive drug use is associated with an increased risk of enteric infection after adjusting for potential biases and confounders.

• H2-receptor antagonists
• enteric infection
• proton pump inhibitor

• Cardiac surgery
• Duodenal ulcer
• Gastrointestinal bleeding
• Proton pump inhibitors

• Angiotensin Receptor Antagonists/therapeutic use
• Angiotensin-Converting Enzyme Inhibitors/therapeutic use
• Cohort Studies
• Humans
• Pneumonia, Viral
• Retrospective Studies

• chronic obstructive pulmonary disease
• pharmacoepidemiology
• pharmacy
• proton pump inhibitor

Background: Recent studies have suggested that proton pump inhibitors (PPIs) and histamine type 2 receptor antagonists (H2RAs) may increase the risk of fracture. We performed a meta-analysis to evaluate the risk of fracture with PPIs and H2RAs use in children and young adults.

Methods: PubMed, EMBASE database, Cochrane Library, and Web of Science for relevant articles published before May 2021 were searched. We included all the observational studies reporting on the risk of fracture with acid-suppressive drug (PPIs and H2RAs) use in children and young adults. We calculated pooled risk ratios (RRs) for fracture using random-effects models and conducted subgroup analyses.

Results: A total of six studies were included in our analysis. Pooled analysis of PPIs use showed significant risk for fracture (RR = 1.23; 95% CI, 1.12–1.34; I² = 79.3), but not significant for PPIs combined with H2RAs use (RR = 1.22; 95% CI, 0.94–1.60; I² = 44.0%), as well as for H2RAs use alone (RR = 1.08; 95% CI, 0.94-1.24; I² = 84.1%). Grouping of studies by region showed a significantly increased fracture risk with PPIs use in North America (RR = 1.24; 95% CI, 1.16–1.32; I² =0.0%) than in Europe (RR = 1.23; 95% CI, 1.00–1.52; I² = 94.6%) and Asia (RR = 1.10; 95% CI, 0.96–1.25). However, there was no significant association between the H2RAs use and the fracture risk in North America (RR = 1.08; 95% CI, 1.00–1.09; I² = 0.0%). Moreover, PPIs use showed an increased risk of fracture in women (RR = 1.13; 95% CI, 1.07–1.19; I² = 0.0%), whereas there was no significant association between the PPIs use and the risk of fracture in men (RR = 0.93; 95% CI, 0.66–1.31; I² = 0.0%).

Conclusion: PPIs use alone could increase the risk of fracture in children and young adults, but not for PPIs combined with H2RAs use or H2RAs use alone. Clinicians should exercise caution when prescribing PPIs for patients.

• fracture
• histamine-2 receptor antagonists
• medication
• meta-analysis
• proton pump inhibitors

• de-implementation
• hospital
• proton pump inhibitor (PPI)
• stress ulcer prophylaxis (SUP)
• systematic review

Proton pump inhibitors (PPIs) are among the most prescribed medications and are often used unnecessarily. PPIs are used for the treatment of heartburn and acid-related disorders. Emerging evidence indicates that PPIs are associated with serious adverse events, such as increased risk of Clostridioides difficile infection. In this study, we designed and piloted a PPI de-implementation intervention among hospitalized non-intensive care unit patients.

Using the Systems Engineering Initiative for Patient Safety (SEIPS) model as the framework, we developed an intervention with input from providers and patients. On a bi-weekly basis, a trainee pharmacist reviewed a random sample of eligible patients’ charts to assess if PPI prescriptions were guideline-concordant; a recommendation to de-implement non-guideline-concordant PPI therapy was sent when applicable. We used convergent parallel mixed-methods design to evaluate the feasibility and outcomes of the intervention.

During the study period (September 2019 to August 2020), 2171 patients with an active PPI prescription were admitted. We randomly selected 155 patient charts for review. The mean age of patients was 70.9 ± 9 years, 97.4% were male, and 35% were on PPIs for ≥5 years. The average time (minutes) needed to complete the intervention was as follows: 5 to assess if the PPI was guideline-concordant, 5 to provide patient education, and 7 to follow-up with patients post-discharge. After intervention initiation, the week-to-week mean number of PPI prescriptions decreased by 0.5 (S<0.0001). Barriers and facilitators spanned the 5 elements of the SEIPS model and included factors such as providers’ perception that PPIs are low priority medications and patients’ willingness to make changes to their PPI therapy if needed, respectively. Ready access to pharmacists was another frequently reported facilitator to guideline-concordant PPI. Providers recommended a PPI de-implementation intervention that is specific and tells them exactly what they need to do with a PPI treatment.

In a busy inpatient setting, we developed a feasible way to assess PPI therapy, de-implement non-guideline-concordant PPI use, and provide follow-up to assess any unintended consequences. We documented barriers, facilitators, and provider recommendations that should be considered before implementing such an intervention on a large scale.

The online version contains supplementary material available at 10.1186/s43058-021-00161-6.

• COVID-19
• Mortality
• Proton pump inhibitors
• SARS-CoV-2, Severity